(1) Field of the Invention
The present invention relates generally to reaction pathways and processes for chemical conversion of amino acids and amides to selective conversion products. More particularly, the present invention relates to selective chemical reaction of L-glutamic acid [CAS no. 56-86-0] and L-pyroglutamic acid [CAS no. 98-79-3] and other related compounds yielding intermediate and end-use products at greater-than-expected yields. Such compounds find applications in such commercial products as solvents, plastics, epoxies, coatings, and urethanes.
(2) Background
Metal catalyzed hydrogenation reactions in the presence of acid at low pH have been shown in several early seminal publications. FIGS. 1a–1c illustrate conversion products stemming from the pioneering work of Adkins et al. (FIG. 1a), Carnahan et al. (FIG. 1b), and Broadbent et al. (FIG. 1c). Adkins et al. (J. Am. Chem. Soc., 1934, 56, p. 689) used various transition metal oxides including those of nickel, copper, and chromium to reduce carboxylic acid esters to alcohols, including, as illustrated in FIG. 1a, conversion of butyl lactate to propylene glycol. Adkins et al. (J. Am. Chem. Soc., 1938, 60, p. 402) later reported reduction of amides via hydrogenation reactions in which Cu—Cr oxide catalysts were used and reduction of a lactam carbonyl using a ruthenium catalyst. Results showed reduction of amides in water typically yields amines whereas reduction of lactams yields alcohols. Carnahan et al. (J. Am. Chem. Soc., 1955, 77, p. 3766) demonstrated conversion of di-carboxylic acids to diols using a ruthenium metal catalyst, as illustrated in FIG. 1b. Broadbent et al. (J. Am. Chem. Soc., 1959, 24, p. 1847) later used a rhenium “black” catalyst to deaminate and hydrogenate amino acids yielding aliphatic alcohols, as illustrated in FIG. 1c. 
The stereo-specific hydrogenation of amino acids has also been reported in the prior art. U.S. Pat. Nos. (5,536,879), (5,731,479), and (6,310,254) assigned to Bayer disclose hydrogenation reactions involving amino acids requiring conditions of low solution pH, extremely high ruthenium oxide/rhenium oxide (RuO2/Re2O7) catalyst loading, large hydrogen partial pressures (3000 psi), prolonged reaction times (e.g., 8 hours), and reaction temperatures near 70° C. Product yields for the conversion products glutamic acid and pyroglutamic acid were reported to be 58% and 65%, respectively, with an enantiomeric excess approaching 98.3%.
In more recent work by Miller et al. [Organic Letters, 2003, 5(4), p. 527], the conversion of alanine to desired products stresses the importance of performing hydrogenations at low pH such that the amino acid is in protonated form rather than carboxylate form. Miller et al. further disclose conditions of a 5% ruthenium metal catalyst and partial hydrogen pressures of 6.9 Mpa (1000 psi). Under neutral pH conditions the zwitterion is not reported to reduce to a functional moiety of interest and favorable reduction of amino acids is minimal.
In general, the prior art teaches that reactions to reduce amino acids require a low solution pH in conjunction with high catalyst loading, prolonged reaction times, and large hydrogen partial pressures. The present invention demonstrates novel pathways and conditions not taught or suggested in the literature for converting amino acids, amides, and substituted amides to highly desirable intermediate and end-use products at high selectivity and high yield.